Prognostic biomarkers of antipsychotic-induced weight gain

Antipsychotic drugs (APs) are used to treat psychiatric disorders but also have the prominent side effect of weight gain resulting in a higher incidence of metabolic disease in this patient group. While the majority of patients gain significant weight in response to APs some patients are relatively resistant to these effects. APs such as clozapine and olanzapine are deemed to be highly efficacious at treating psychiatric conditions yet they have some of the highest weight gain liabilities. Therefore, there is a need to determine which patients are less susceptible to the metabolic side effects of APs and would be good candidates for drugs such as olanzapine, and conversely, identifying patients that should be prescribed alternative APs with less weight gain liabilities. The C57BL/6 female mice (stock #000664) were purchased from Jackson Laboratory at 9 weeks of age. Blood was collected, RNA was extracted, and stored at -80°C. The mice were fed normal chow diet until 10 weeks of age, when the mice were transitioned to a high fat diet (HFD) (45% kcal from fat) for 3 days to acclimatize to the caloric density. Mice were then fed a formulation of 45% HFD with olanzapine incorporated into HFD (Research Diets, Inc., D09092903). All mice were singly housed throughout the study, and food intake was measured daily, and body weight was measured every other day for 14 days. At the end of the study, mice were anesthetized and sacrificed. Blood was collected and processed for RNA collection.